Abstract
BackgroundIn 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has re-emerged as an adjuvant therapeutic strategy. We conducted a systematic review and meta-analysis to assess the evidence for the effect of surgery as an adjunct to chemotherapy on outcomes of adults treated for MDR-TB.MethodsDatabases and grey literature sources were searched using terms incorporating surgery and MDR-TB. No language or publication type limits were applied. Articles published pre-1990, without a comparator group, or reporting <10 surgical participants were excluded. Two-stage sifting in duplicate was employed. Data on WHO-defined treatment outcomes were abstracted into a standardised database. Study-level risk of bias was evaluated using standardised tools. Outcome-level evidence quality was assessed using GRADE. Forest plots were generated, random effects meta-analysis conducted, and heterogeneity assessed using the I2 statistic.ResultsOf 1024 unique citations identified, 62 were selected for full-text review and 15 retained for inclusion. A further four articles were included after bibliography/citation searching, and one additional unpublished manuscript was identified, giving 20 articles for final inclusion. Six were meta-analyses/systematic reviews and 14 were primary research articles (observational studies).From the 14 primary research articles, a successful outcome (cured/treatment completed) was reported for 81.9 % (371/453) and 59.7 % (1197/2006) in the surgical and non-surgical group respectively, giving a summary odds ratio of 2.62 (95 % confidence interval 1.94–3.54). Loss to follow-up and treatment failure were lower in the surgery group (both p = 0.01). Overall GRADE quality of evidence for all outcomes considered was “very low”.ConclusionsThis meta-analysis suggests that surgery as an adjunct to chemotherapy is associated with improved treatment outcomes in MDR-TB patients. However, inherent limitations in observational study design, insufficient reporting, and lack of adjustment for confounders, led to grading of the evidence as very low quality. Data on rationale for surgical referral, subsequent outcomes and resource-limited settings are scarce, precluding evidence-based recommendations on the suitability of surgery by patient characteristics or setting. It is hoped that highlighted methodological and reporting gaps will encourage improved design and reporting of future surgical studies for MDR-TB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1585-0) contains supplementary material, which is available to authorized users.
Highlights
In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-extensively drug resistant tuberculosis (TB)) patients achieved a successful treatment outcome
It is estimated that 20 % of previously treated TB cases and 3.3 % of new TB cases worldwide have multidrug-resistant tuberculosis (MDR-TB), which is caused by bacterial strains resistant to both the two major anti-tuberculosis drugs, isoniazid and rifampicin [1]
The research question explored surgery as an adjunct to standard of care, the comparator group was defined as those patients who received second-line chemotherapy including at least four drugs, and the intervention was defined as surgery in addition to this standard of care
Summary
In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. Treatment for MDR- and XDR-TB currently entails therapeutic regimens with much lower efficacy and much greater toxicity than those used for drug-susceptible TB. Recommended treatment requires at least 20 months of therapy and in 2014 only 50 % of MDR-TB patients globally had a successful treatment outcome compared to 86 % for newly diagnosed drug susceptible disease. Even with the discovery of bedaquiline and delamanid, the first antituberculosis drugs with new mechanisms of action to be approved in over 40 years and the first drugs to be introduced for MDR-TB combination therapy [2,3,4], access is limited and regimen effectiveness still remains below that of drug susceptible disease [4, 5]. Increasing drug resistance further limits the treatment options available to MDR-TB patients
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